Remdesivir-Associated Acute Liver Failure in a COVID-19 Patient: A Case Report and Literature Review

Ahmed-Khan, Mohammad A; Matar, George; Coombes, Kyle; Moin, Kayvon; Joseph, Bishoy M; Funk, Carly M

doi:10.7759/cureus.34221

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…Some of them have a number of side effects, incl. potential mutagenicity for the host 22 and death 23 …”

Section: Discussionmentioning

confidence: 99%

“…potential mutagenicity for the host 22 and death. 23 WHO recommends medications that inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, the interleukin-6 receptor, and the tyrosine kinase Janus kinase. 18 Our treatment strategy targets the inhibition of SARS-CoV-2 entry into the cell and the NLRP3 inflammasome, as the source of the CS.…”

Section: Two Different Strategies For Treating Covid-19mentioning

confidence: 99%

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Effect of increasing doses of colchicine on the treatment of 333 COVID‐19 inpatients

Tiholov,

Lilov,

Georgieva

et al. 2024

Immunity Inflam & Disease

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BackgroundPrevious research done in Bulgaria demonstrated a fivefold reduction in mortality from COVID‐19 with increased doses of colchicine from two hospitals in the country. We report here a further 333 cases of COVID‐19 inpatients, treated with different doses of colchicine and its effect on mortality.Materials and MethodsA case‐control comparison from two additional hospitals was conducted between increased doses of colchicine and added bromhexine to standard of care (SOC) versus current SOC. Risk and odds ratio, as well as subgroup analysis, was conducted with newly reported data, alongside aggregate data from all hospital centers to determine the extent of mortality reduction in COVID‐19 inpatients.ResultsThere was a clear reduction in the mortality of inpatients with increasing doses of colchicine—between twofold and sevenfold. Colchicine loading doses of 4 mg are more effective than those with 2 mg. Despite these doses being higher than the so‐called “standard doses,” colchicine inpatients experienced lower mortality than SOC patients (5.7% vs. 19.53%). This mortality benefit was evident in different age subgroups, with a 4‐mg loading dose of colchicine proving slightly superior to a 2‐mg loading dose. Colchicine led to an overall relative risk reduction of 70.7%, with SOC patients having 3.91 higher odds of death. The safety of the doses was not different than the reported in the summary of product characteristics.ConclusionInpatients in Bulgaria with added colchicine and bromhexine to SOC achieved better clinical and mortality outcomes than those on SOC alone. These results question the World Health Organization—recommended strategy to inhibit viral replication. We posit that our treatment strategy to inhibit the Severe acute respiratory syndrome coronavirus 2 entry into the cell with inhaled bromhexine and the hyperactivated NLRP3 inflammasome with higher doses of colchicine, prevents the development of cytokine storm. The timing of the initiation of treatment seems critical.

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“…Some of them have a number of side effects, incl. potential mutagenicity for the host 22 and death 23 …”

Section: Discussionmentioning

confidence: 99%

Section: Two Different Strategies For Treating Covid-19mentioning

confidence: 99%

Effect of increasing doses of colchicine on the treatment of 333 COVID‐19 inpatients

Tiholov,

Lilov,

Georgieva

et al. 2024

Immunity Inflam & Disease

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“…Several studies have highlighted that there are no absolute contraindications if liver function is closely monitored during treatment [ 60 , 61 ]. Despite a few case reports of suspected remdesivir-associated acute liver failure [ 62 , 63 , 64 ], IDSA guidelines suggest the administration of remdesivir also in hospitalized patients with mild to moderate COVID-19 with a high risk of progression and in patients with severe COVID-19, paying attention to the liver function test. In ambulatory patients, ritonavir could also induce mild to moderate elevation in aminotransferases and cholestasis [ 65 , 66 ].…”

Section: Management Of Covid-19 In Subjects With Fldmentioning

confidence: 99%

COVID-19 and Fatty Liver Disorders

Guarino

Cossiga

Cutolo

et al. 2023

JCM

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In late 2019, the world was shaken by the COVID-19 pandemic. Severe Acute Respiratory Syndrome Coronavirus—2 (SARS-CoV-2) infection became one of the main causes of illness and hospitalization worldwide, especially in subjects with metabolic comorbidities such as obesity, diabetes, or liver disease. This scenario crosses with the metabolic liver disorders’ “pandemic”, caused by the exponential spreading of non-alcoholic fatty liver disease, which is now the most prevalent cause of chronic liver disease (CLD). The aim of this review is to analyze the key factors of the relationship between COVID-19 and the spectrum of fatty liver disorders (FLD), in terms of molecular mechanisms and clinical presentation which can predict a more severe course of the infection. In addition, this review will face the change in management of FLD during pandemics, with a central role of telemedicine, and the role of other interventions in preventing and treating severe infection in these subjects.

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“…In early 2020, RDV was approved by the US Food and Drug Administration (FDA) as the first antiviral agent for the treatment of COVID-19 patients requiring hospitalization (Lamb, 2020). Pharmacovigilance data however revealed that clinical use of RDV is associated with potential risk of hepatic adverse drug reactions and monitoring serum levels of ALT and AST has been a required practice in RDV-based COVID-19 treatment (Ahmed-Khan et al, 2023;Aleem et al, 2021;Sadaf et al, 2023). With the rapid evolution of the disease, co-administration of RDV and dexamethasone (DEX) was soon updated as a standard care in the new treatment guideline for hospitalized COVID-19 patients requiring respiratory support (Benfield et al, 2021;Mehta et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Understanding of Dexamethasone-Mediated Protection against Remdesivir-Induced Hepatotoxicity

Liu,

Li,

et al. 2024

Mol Pharmacol

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Remdesivir (RDV), a broad-spectrum antiviral agent, is often used together with dexamethasone (DEX) for hospitalized COVID-19 patients requiring respiratory support. Potential hepatic adverse drug reaction is a safety concern associated with the use of RDV. We previously reported that DEX co-treatment effectively mitigates RDV-induced hepatotoxicity and reduces elevated serum ALT and AST levels in cultured human primary hepatocytes (HPH) and hospitalized COVID-19 patients, respectively. Yet, the precise mechanism behind this protective drug-drug interaction remains largely unknown. We show here that through the activation of p38, c-Jun Nterminal kinase (JNK), and extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling, RDV induces apoptosis (cleavage of caspases 8, 9, and 3), autophagy (increased autophagosome and LC3-II), and mitochondrial damages (decreased membrane potential, respiration, ATP levels, and increased expression of Bax and the released cytosolic cytochrome C) in HPH. Importantly, co-treatment with DEX partially reversed RDV-induced apoptosis, autophagy, and cell death.Mechanistically, DEX deactivates/dephosphorylates p38, JNK, and ERK1/2 signaling by enhancing the expression of dual specificity protein phosphatase 1 (DUSP1), a mitogen-activated protein kinase (MAPK) phosphatase, in a glucocorticoid receptor (GR)-dependent manner.Knockdown of GR in HPH attenuates DEX-mediated DUSP1 induction, MAPK dephosphorylation, as well as protection against RDV-induced hepatotoxicity. Collectively, our findings suggest a molecular mechanism by which DEX modulates the GR-DUSP1-MAPK regulatory axis to alleviate the adverse actions of RDV in the liver.

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Remdesivir-Associated Acute Liver Failure in a COVID-19 Patient: A Case Report and Literature Review

Cited by 7 publications

References 14 publications

Effect of increasing doses of colchicine on the treatment of 333 COVID‐19 inpatients

Effect of increasing doses of colchicine on the treatment of 333 COVID‐19 inpatients

COVID-19 and Fatty Liver Disorders

Mechanistic Understanding of Dexamethasone-Mediated Protection against Remdesivir-Induced Hepatotoxicity

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